The National Standard for Normal Fetal Growth

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

ClinicalTrials.gov Identifier:

NCT00912132

First Posted: June 3, 2009

Last Update Posted: October 26, 2017

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Normal fetal growth is a critical component of a healthy pregnancy and the long-term health of the offspring. Pivotal to understanding the dynamics of human fetal growth and to defining normal and abnormal fetal growth is the development of standards for fetal growth. The study's purpose was to establish standards for normal fetal growth and size for gestational age for 4 racial/ethnic groups of pregnant women with the eventual creation of individualized standards for fetal growth and improvements in fetal weight estimation. These data for a contemporary cohort of pregnant women should provide data for clinical management.

Fetal growth trajectories were created using linear mixed models with cubic splines for estimating racial/ethnic specific fetal growth curves for size, methods that accounted for the variation across individual fetuses. For EFW and each individual anthropometric parameter, we tested for overall differences in the racial/ethnic-specific curves using a likelihood-ratio test. When the global test was significant (<.05 level), we tested for week-specific differences by race/ethnicity using Wald tests at each week of gestation. These tests were conducted on the estimated curves with and without adjustment for maternal characteristics.

A fetal growth velocity standard by maternal race/ethnicity was also created.

Create an individualized standard for fetal growth potential.

Individualized and customized fetal growth models will be created using two- dimensional ultrasound measures. Individualized or customized definitions of small for gestational age or large for gestational age will be compared to the NICHD Fetal Growth Study singleton standard cut-points of 10th and 90th percentiles, respectively, to see if they improve detection of maternal and neonatal health outcomes.

Improve accuracy of fetal weight estimation.

Since the last ultrasound exam is scheduled at term, it was expected that many women would deliver within 3 days after the last ultrasound exam. A formula (or formulas) to estimate fetal weight will be created using a multiple linear regression to include not only the 2-D and 3-D sonographic measurements but also factors such as maternal height and weight, sex of the fetus, and glucose challenge test result. We will identify a formula that provides the best estimate of fetal weight, and apply that formula to a validation group. If the sample size allows, we will randomly split the whole cohort into two groups: one group for testing and the other for validation. If the statistical power is insufficient for splitting, we will use cross-validation.

Secondary Outcome Measures:

Construct an individualized standard for fundal height.

We will reevaluate the sensitivity and specificity of the current approach to using fundal height to monitor fetal growth. We will produce an individualized standard for fundal height. We will compare the new standard with the current approach with regard to true positive and true negative values.

Collect blood samples for an etiology study of gestational diabetes and a prediction study of fetal growth restriction and/or overgrowth.

Women with singleton gestations were enrolled between 8w0d and 13w6d and followed up to nine months (2009-2013) in this prospective cohort study. A sub-set of women with and without gestational diabetes were followed up to 6 weeks postpartum. Enrollment was based upon a predefined set of criteria including medical/reproductive history and pre-pregnancy body mass index. Women with a body mass index between 19.0-29.9 kg/m2 were in the low-risk cohort.

Obese cohort

Women with singleton gestations were enrolled between 8w0d and 13w6d and followed up to nine months (2009-2013) in this prospective cohort study. A sub-set of women with and without gestational diabetes were followed up to 6 weeks postpartum. Enrollment was based upon a predefined set of criteria including medical/reproductive history and pre-pregnancy body mass index. Women with a body mass index between 30.0-44.9 kg/m2 were in the obese cohort.

Detailed Description:

Summary and aims:

Normal fetal growth is a critical component of a healthy pregnancy and the long-term health of the offspring. Pivotal to understanding the dynamics of human fetal growth and to defining normal and abnormal fetal growth is the development of standards for fetal anthropometric parameters measured longitudinally throughout gestation, which, in turn, can be used to develop interval velocity curves and customized for genetic and physiological factors. We propose to conduct a multi-center prospective observational study (1) to establish a standard for normal fetal growth (velocity) and size for gestational age in the U.S. population; (2) to create an individualized standard for fetal growth potential; and (3) to improve accuracy of fetal weight estimation.

Eligibility:

• Healthy, low-risk pregnant women (both obese and nonobese) between the ages of 18 and 40 from each of the following four self-identified race/ethnicity backgrounds: African American, Asian, Caucasian, and Hispanic.

Design:

Observational cohort design where pregnant women are recruited prior to 13 weeks gestation and followed throughout pregnancy and delivery for women having livebirths.

An enrollment interview was followed by depression screening, physical activity, anthropometric assessment and ultrasonology screening for measurement of fetal growth, and at each of the 5 subsequent visits.

Women were asked to provide blood samples at enrollment and at follow-up visits at 16-22 weeks, 24-29 weeks, and 34-37 weeks of gestation.

Neonatal anthropometry completed for all infants within 12-24 hours after birth.

Cord blood, plasma, and placenta samples were collected for a smaller subsample of newborns.

Post-study evaluations: Women who were diagnosed with gestational diabetes during pregnancy were asked to return for a follow-up visit 6 weeks after delivery.

Enrollment:

Final recruitment included 2,802 women with singleton pregnancies of which 2,334 were healthy, low-risk women with pre-pregnancy body mass indices (BMI) between 19-29.9 kg/m2. The racial/ethnic distribution of participating women were: Caucasians (n=614), African American (n=611), Hispanics (n=649), and Asians (n=460), and reflects natality characteristics of contemporary U.S. births. An additional 468 obese women (BMI 30-44.9 kg/m2) were also recruited.

Quality Control:

The quality of the ultrasound measures was guaranteed by implementation of: (1) a comprehensive quality control protocol for ante hoc training and credentialing of all site sonographers, developed by the sonology center at Columbia University, and (2) a rigorous protocol for post hoc quality control, whereby a random sample of all scans, stratified by clinical site and visit, was re-measured for accuracy and reliability.

Eligibility

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Ages Eligible for Study:

18 Years to 40 Years (Adult)

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Sampling Method:

Non-Probability Sample

Study Population

Women with singleton gestations (n=2,802) were enrolled from 12 U.S. clinical centers. Women were enrolled between 8w0d and 13w6d gestation, as measured by last menstrual period dating consistent with obstetrical ultrasonology.

LMP-date and ultrasound date match within 5 days for gestation estimates between 8 weeks + 0 days and 10 weeks + 6 days, 6 days for those between 11 weeks + 0 days and 12 weeks + 6 days, and 7 days for estimates between 13 weeks + 0 days and 13 weeks + 6 days

No confirmed or suspected fetal congenital structural or chromosomal anomalies

Pregnancy and postpartum data will be made accessible in documented repositories and electronic archives after completion of the studies' analytical phases.

Time Frame:

After completion of the studies' analytical phases.

Access Criteria:

The data, along with a set of guidelines for researchers applying for the data, will be posted to a data-sharing site. All requests for data must include a short protocol with a specific research question and a plan for analysis. Before receiving any analytical file, all users must complete a Data Use Agreement form.